Asbestos A Potent And Established Carcinogen

Animal and human epidemiologic studies indicate that inhalation of asbestos can cause serious respiratory diseases, including asbestosis, bronchogenic cancer, and mesothelioma.137 138 Exposure to asbestos has also been linked to certain types of tumors that originate in the stomach, throat, and rectum.139 People who are working with asbestos-containing products or who live near asbestos mining/manufacturing areas also have a high risk of contracting asbestos-induced lung diseases.140

Asbestos refers to a family of crystalline fibrous silicates that are relatively indestructible, heat resistant, and have a high commercial importance. Serpentines and amphiboles are the two distinct varieties of asbestos with succinct physical and chemical characteristics of commercial importance in different applications. The serpentine asbestos (chrysotile) is curly and flexible and accounts for most of the asbestos used commercially in North America. Crocidolite, amosite, tremolite, and anthophilite are the important commercial amphiboles, but these are used less frequently than chrysotile. Amphiboles are straight, rodlike fibers. The relative toxicity, pathogenicity, and carcinogenicity of these different types of asbestos have been extensively investigated both in animal and human studies. Epidemiologic data of human asbestos exposure suggest that amosite and crocidolite forms of asbestos are more pathogenic and carcinogenic than chrysotile, particularly in reference to induction of mesotheliomas.141 Such potency may be largely due to their needlelike shape that hinders the clearance of these fibers from the lung. The chrysotile asbestos is considered less carcinogenic because of its curly shape, which is likely to cause impaction in the upper airways, which facilitates mucociliary clearance. Some studies of chrysotile workers have reported a few mesotheliomas. It has been suggested that these mesotheliomas are likely due to contamination of chrysotile with the amphibole, tremolite. However, animal studies indicate that all forms of asbestos are equally carcinogenic, and there is a clear dose-response relationship.137

The mechanism of asbestos-induced carcinogenesis is still a debatable issue. Inhaled asbestos fibers in alveoli can be phagocytized by alveolar macrophages.4 For occupational exposures to long, thin fibers, several phagocytes are often found attempting to phagocytize a single long fiber. One plausible mechanism of asbestos-induced carcinogenesis is its ability of sustained induction of ROS that cause DNA strand breaks and deletion mutations. In addition, asbestos can also alter the normal intracellular signal transduction pathways by increased autophosphorylation of the EGF receptor, leading to activation of downstream kinases and transcription factors, such as AP-1 and NF-kB. Furthermore, asbestos is capable of depressing immune function by stimulating macrophages to produce immune suppressive lymphokines and other mediators.

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